Author + information
- Giovanna Liuzzo,
- Davide Flego,
- Giulia Angelini,
- Ramona Vinci,
- Daniela Pedicino,
- Giuseppe Piemontese,
- Francesco Trotta,
- Anna Severino,
- Ada F. Giglio,
- Luigi Biasucci and
- Filippo Crea
Background: T-cells in acute coronary syndromes (ACS) show reduced expression and activity of the immunomodulatory molecule CD31 compared to patients with stable angina (SA). In T-cells, the shedding of the CD31 functional domains 1 to 5 leads to uncontrolled lymphocyte activation. A recent experimental work suggests a role for the matrix metalloproteinase 9 (MMP9) in CD31 cleavage. Of note, ACS patients have higher serum levels of MMP9. Aim of the study is investigate the role of MMP9 in CD31 cleavage in ACS patients.
Methods: We performed flow cytometry experiments on CD4+ T-cells of 36 ACS and 33 SA patients. We used two different CD31 antibodies that specifically recognize CD31 functional domains 1-5 (WM59 clone) or CD31 membrane-proximal domain 6 (MBC 78.2 clone). We performed the same experiments after TCR-stimulation with aCD3/aCD28 (N=8 for each group). ELISA was performed to evaluate MMP9 production from activated T-cells and MMP9 inhibition experiments were carried out on TCR-stimulated CD4+ T-cells.
Results: CD31 functional domains 1-5 surface expression on Naïve and Memory T-cells, was higher in SA than in ACS (Naïve: 1.97± 0.16 vs 1.61 ± 0.12 P=0.001; Memory: 2.1±0.16 vs 1.54±0.09, P=0.05). The ratio between CD31 functional domains 1-5 and CD31 domain 6 expression was significantly higher in SA than in ACS (Naïve: 0.9± 0.05 vs 0.7±0.03 P=0.002; Memory: 0.9±0.06 vs0.7±0.05 P=0.02) After 6 days of stimulation with anti-CD3/CD28 crosslink, the expression of CD31 domains 1-5 was higher in SA than in ACS (4.4±0.5 vs 2.6±0.3 P=0.012). No differences were observed in CD31 domain 6 expression. After TCR-stimulation, T-cell supernatants showed higher release of MMP-9 in ACS than in SA (507.1 ± 97.62 vs 193.0 ± 36.59, P=0.02). Using MMP-9 inhibitor, we observed an increase in CD31 domains 1-5 expression on CD4+ T-cells of ACS patients (3.15±1.9 vs 1.4±0.3 P=0.04).
Conclusions:In our study, a higher production of MMP-9 by TCR-stimulated T-cells from ACS patients resulted in lower expression of CD31 functional domains 1-5 as result of an increased shedding, thus leading to uncontrolled lymphocyte activation. Our data expand previous findings, opening the way to novel therapeutic strategies in ACS.
Poster Hall, Hall C
Friday, March 17, 2017, 3:45 p.m.-4:30 p.m.
Session Title: Biomarkers and Targets for Ischemic Heart Disease
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1164-302
- 2017 American College of Cardiology Foundation